Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats

<p><span>Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease. Despite therapeutic advances, a significant proportion of RA patients are resistant to pharmacological treatment. Stimulation of the cervical vagus nerve is a promising alternative bioelectric neuromodulation therapeutic approach. However, recent clinical trials show cervical vagus nerve stimulation (VNS) was not effective in a significant proportion of drug-resistant RA patients. Here we aim to assess if abdominal vagus nerve stimulation reduces disease severity in a collagen-induced arthritis (CIA) rat model.</span><span> The abdominal vagus nerve of female Dark Agouti rats was implanted and CIA-induced using collagen type II injection. VNS (</span><span>1.6 mA, 200 µs pulse width, 50 µs interphase gap, 27 Hz frequency)</span><span> was applied to awake freely moving rats </span><span>for 3 h/day (</span><span>days 11–17). A</span><span>t 17 days following the collagen injection,</span><span> unstimulated CIA rats (n = 8) had significantly worse </span><span>disease activity index, </span><span>tumour necrosis factor-alpha (</span><span>TNF) and </span><span>receptor activator of NF</span><span>k</span><span>B ligand (</span><span>RANKL) levels, synovitis and cartilage damage than normal rats (n = 8, </span><span>Kruskal-Wallis:</span> <span><em>P</em> </span><span>&lt; 0.05). However, </span><span>stimulated CIA rats (n = 5-6) had significantly decreased inflammatory scores and ankle swelling (Kruskal-Wallis: </span><span>P</span><span> &lt; 0.05) compared to unstimulated CIA rats (n = 8). Levels of tumour necrosis factor-alpha (TNFα) remained at undetectable levels in stimulated CIA rats while levels of receptor activator of NF</span><span>k</span><span>B ligand (RANKL) were significantly less in stimulated CIA rats compared to unstimulated CIA rats (</span><em><span>P</span></em><span> &lt; 0.05). Histopathological score of inflammation and cartilage loss in stimulated CIA rats were no different from that of normal (</span><span><em>P</em> </span><span>&gt;</span><span> 0.05). In conclusion, abdominal VNS alleviates CIA and could be a promising therapy for patients with RA.</span></p>